Implanted medical devices such as venous and arterial catheters, neurological prostheses, wound drains, urinary “Foley” catheters, peritoneal catheters, and other luminal in-dwelling devices, have been useful for treating various medical conditions. However, a drawback of implanted medical devices is the risk of infection while the medical device is inserted in the body, and thereafter. Such risk exists even though the medical devices are sterilized and carefully packaged to guard against introduction of microbes or pathogens during implantation or insertion of the medical device. For example, there is a risk of serious nosocomial infections when using catheters for hemodialysis procedures. In fact, central venous catheters account for most nosocomial catheter-related bloodstream infections.
When catheters and other in-dwelling luminal devices are inserted into body cavities such as the urinary tract, venous or arterial vessels, bacteria or other microbes can be picked up from the skin and carried into the insertion site where bacterial or microbial colonization may ensue. Infections may derive from an interaction of the microbes and the catheter micro-surface. Once infected, the microorganisms adhere to the catheter micro-surface and rapidly become encased in a polysaccharide matrix or biofilm, which protects the microorganisms from a host's defenses.
In the case of urinary and venous catheters, there is a significant threat of microbial growth along the exterior surface or outer wall of the catheter and, especially for catheters used long-term, there is a significant threat of microbial growth along the interior surface or inner wall. This can lead to chronic urinary tract infections (CUTI), or septicemia in the case of venous and arterial catheters, thrombolytic emboli, stenosis, and thrombosis resulting from infections, and other life threatening complications, especially among the elderly and immuno-compromised patients. Thus, there is a need for the development of better methods of preventing and treating infections caused by the insertion of catheters into a patient's body.
There have been many attempts to prevent such infections. For example, central venous catheters have been developed with chlorohexidine and silver sulfadiazine coatings (ArrowG+ard) and with a combination of minocycline and rifampin coatings (see, e.g., Cook Spectrum™). However, these antiseptic/antibiotic-impregnated catheters have not been adequate, as they have only been shown to reduce the incidence of catheter related infections in the short term, such as less than 14 days. Thus, there is a need for improved catheters that are effective in reducing infections in the long-term.
Iodine-based interventional devices have also been used to minimize the risk of nosocomial bloodstream infection. In particular, an iodine-based, soft, flexible poly-carbonate fiber in the shape of a rod has been placed inside of in-dwelling catheters, as discussed in WO 00/74743 A1. Generally, these polymeric-matrices are chemically and geometrically configured to enable a controlled-release of monomeric iodine at specific conditions such as temperature, making them extremely useful as anti-infective substrates for the effective management of catheter-based nosocomial blood stream infections. Since the catheter polymer is semi-permeable, the iodine can egress to the exterior surface of the in-dwelling catheter.
Such iodine-loaded rod is inserted into a catheter by gently sliding the rod into the inlet and outlet ports of a lumen of the catheter through which body fluids flow. During insertion, the rod is held between the thumb and index fingers of the person inserting the rod. Due to the flexibility of the rod, resistance may be encountered while gently threading it into the lumen. Inserting this rod into the catheter, without contamination, is an arduous and challenging exercise. Even with the use of gloves, there is a potential for contamination. Also, during a dialysis treatment, the iodine rod has to be removed from the lumen through which body fluid flows. New iodine rods are inserted after completion of this dialysis. With multiple insertions and removals of the rods from the lumen, which is in contact with body fluids, there is an increased risk of contamination. It would be desirable to have a medical device comprising an anti-microbial substrate that would not have to be removed and reinserted during every dialysis treatment, and which is not in contact with body fluids, i.e., independent of the inlet and outlet lumens.
However, generally, the distal tips of catheters have open ends so that body fluid such as blood can enter and exit the catheter lumens. Use of iodine rods with such catheters having open ends can be problematic. For example, blood clots could form at the open ends of the catheter tip and hinder the insertion of the iodine rod. In addition, iodine is directly released into the body or bloodstream through the open tip. Thus, it would be desirable to have a catheter designed to be effectively used with a substrate having anti-microbial properties. It would also be desirable to prevent iodine in the lumen from escaping directly through the open catheter tip and into the body, yet deliver iodine into the inlet and outlet lumens. Moreover, it would be desirable to be able to control the release of iodine into the body.
Accordingly, there is a need for a medical device that has a portion that can be inserted into the body of a patient and that can more effectively provide anti-microbial activity. In particular, there is a need for a medical device that can provide anti-microbial properties without requiring repeated insertions and removals of an anti-microbial substrate that could introduce contamination. There is also a need for a medical device that can provide long-term anti-microbial or anti-infection activity. There is also a need for an improved method of making such medical devices.